Wade A E, Evans J L, Seitz A
Pharmacology. 1976;14(2):104-14. doi: 10.1159/000136586.
The administration of a diet deficient in thiamin results in elevated hepatic microsomal activity of aniline hydroxylase, ethylmorphone demethylase, NADPH cytochrome c reductase and cytochrome P-450 when compared to similar female rats fed diets supplemented with thiamin. Accompanying these differences in enzyme activity are increased concentrations of microsomal docosahexaenoic acid and arachidonic acid. Binding of aniline to microsomes from rats fed high levels of thiamin is decreased due to a decrease in cytochrome P-450. On the other hand, the binding of ethylmorphine to P-450 is decreased by feeding high levels of thiamin. The daily administration of mestranol enhanced ethylmorphine and aniline metabolism to a greater extent in rats fed thiamin-rich diet than in rats fed thiamin-deficient diet or laboratory chow. This treatment did not increase cytochrome P-450 cytochrome c reductase or microsomal protein nor does it appear to affect the binding of aniline to cytochrome P-450. Ethylmorphine binding is generally decreased by this treatment. Alterations in the Michaelis constants for these reactions were limited to an increase in the Ks for aniline in pair-fed animals and in the Ks for ethylmorphine in thiamin-deficient rats receiving 1.0 mg mestranol per day.
与喂食补充硫胺素饮食的雌性大鼠相比，喂食硫胺素缺乏饮食会导致肝微粒体中苯胺羟化酶、乙基吗啡脱甲基酶、NADPH细胞色素c还原酶和细胞色素P - 450的活性升高。伴随着这些酶活性差异的是微粒体二十二碳六烯酸和花生四烯酸浓度的增加。由于细胞色素P - 450减少，喂食高剂量硫胺素的大鼠微粒体中苯胺的结合减少。另一方面，喂食高剂量硫胺素会降低乙基吗啡与P - 450的结合。与喂食硫胺素缺乏饮食或实验室常规饲料的大鼠相比，每天给予炔雌醇在喂食富含硫胺素饮食的大鼠中更大程度地增强了乙基吗啡和苯胺的代谢。这种处理不会增加细胞色素P - 450、细胞色素c还原酶或微粒体蛋白，也似乎不会影响苯胺与细胞色素P - 450的结合。这种处理通常会降低乙基吗啡的结合。这些反应的米氏常数的变化仅限于成对喂食动物中苯胺的Ks增加以及每天接受1.0毫克炔雌醇的硫胺素缺乏大鼠中乙基吗啡的Ks增加。
